Our co-pending, but as of the priority date, unpublished PCT applications nos PCT/EP02/02328 & PCT/EP02/02346 claim novel NNRTIs of the formula I/II
where:    R1 is O, S;    R2 is an optionally substituted, nitrogen-containing heterocycle, wherein the nitrogen is located at the 2 position relative to the (thio)urea bond;    R2 is an optionally substituted, nitrogen-containing heterocycle, wherein the nitrogen is located at the 2 position relative to the (thio)urea bond;    R3 is H, C1-C3 alkyl,    R4-R7 are independently selected from H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, haloC1-C6 alkyl, C1-C6 alkanoyl, haloC1-C6 alkanoyl, C1-C6 alkoxy, haloC1-C6 alkoxy, C1-C6 alkyloxyC1-C6 alkyl, haloC1-C6 alkyloxyC1-C6 alkyl, hydroxyC1-C6 alkyl, aminoC1-C8 alkyl, carboxyC1-C6 alkyl, cyanoC1-C6 alkyl, amino, carboxy, carbamoyl, cyano, halo, hydroxy, keto and the like;    X is —(CH2)n-D-(CH2)m— or X is —(CRaRb)c—    D is —NR8—, —O—, —S—, —S(═O) or —S(═O)2—    R8 is H, C1-C3 alkyl    Ra and Rb are independently H, C1-C3 alkyl, OH or Ra and Rb together are ═O    n and m are independently 0 or 1;    c is 1, 2 or 3and pharmaceutically acceptable salts and prodrugs thereof.
Although the urea and thiourea NNRTIs disclosed in the above documents are exquisitely active against reverse transcriptase, especially that of HIV-1, the nature of the HIV virus with its extreme lack of replicative fidelity and consequent tendency to rapid resistance development prompts a demand for further antiretroviral agents with enhanced antiviral performance against problematic drug escape mutants, notably at the RT 100, 103 and/or 181 positions.